Chronic Hepatitis CPhase 1NCT01018615
Safety, Metabolism, and Antioxidant Activity of Silymarin and Green Tea Extract in Patients With Chronic Hepatitis C
A Phase 1 study testing silymarin and green tea extract (EGCG) in people with Chronic Hepatitis C and Oxidative Stress, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this study is to determine if the safety, metabolism, and antioxidant activity of silymarin and green tea extract are changed when they are given in combination to patients with chronic hepatitis C infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C, Oxidative Stress
- What is being tested?
- silymarin and green tea extract (EGCG)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Jul 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will be eligible for enrollment in this study if they meet the following criteria:
- Males or females; age at least 18 years at screening
- Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of silymarin. Females of childbearing potential must be using two reliable forms of effective contraception during the study (while on drug and during follow-up)
- Hepatitis C virus (HCV) patients
- Any HCV genotype
- Never been treated or received less than 50% of standard peg-interferon-based therapy.
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- No interferon-based therapy in the previous 6 months
- Serum HCV RNA above quantifiable level of detection by the assay, within 1 year of screening.
- Before entering the study, subjects must agree not to consume alcohol for 48 hours prior to PK sampling days or while on study.
Who cannot join
- Subjects with any of the following will not be eligible for participation:
- Use of other milk thistle or green tea preparations within 30 days of Study Visit 1 (Day 1)
- Use of other antioxidants such as vitamin E, vitamin C, glutathione, alpha-tocopherol, within 30 days of Study Visit 1 (Day 1). A multivitamin at standard doses will be allowed.
- Use of diets containing > 6 servings per day, or 4-6 servings per day from > 8 of the vegetables and fruits listed in Appendix 2.
- Allergy/sensitivity to milk thistle, green tea or their preparations
- Inability to tolerate milk products (lactose intolerant)
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- Use of any interferon-based therapy in the last 6 months.
- Use of warfarin, metronidazole or chronic use of acetaminophen greater than two grams per day
- Previous liver biopsy that demonstrated presence of cirrhosis or previous liver biopsy that demonstrated greater than or equal to 15% steatosis or evidence of steatohepatitis
- Positive test for anti-HIV or HBsAg within 3 years of screening
- Positive urine drug screen for drugs of abuse at screening
- Alcohol consumption of more than one drink or equivalent (>12 grams) per day. Patients who consumed more than this in the past must have maintained a level 12 grams or less per day of alcohol consumption for at least six months prior to screening.
- History of other chronic liver disease, including metabolic diseases, documented by appropriate test(s)
- Women with ongoing pregnancy or breast-feeding, or contemplating pregnancy
- Platelet count <130,000 cells/mm3.
- Creatinine clearance ≤30cc/min or currently on dialysis. Creatinine clearance will be calculated according to Cockcroft-Gault.
- Evidence of alcohol or drug abuse within 6 months prior to screening
- Evidence of decompensated liver disease defined as any of the following: serum albumin <3.2 g/dl, total bilirubin > 1.5 mg/dl, or PT/INR > 1.3 times normal at screening, or history or presence of ascites or encephalopathy, or bleeding from esophageal varices
- History of inflammatory bowel disease or autoimmune hepatitis
- History of solid organ or bone marrow transplantation
- History of thyroid disease poorly controlled on prescribed medications
- Use of oral steroids within 30 days prior to screening
- Concurrent medications that are CYP3A4 inducers
- Inability or unwillingness to provide informed consent or abide by the study protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill- UNC Health Care
Chapel Hill, North Carolina, 27514
About this study
Official title: Steady-State Pharmacokinetic Interactions of Green Tea Catechins and Silymarin Flavonolignans in Treatment Naïve Patients With Chronic Hepatitis C Infection
The purpose of this study is to determine if the safety, metabolism, and antioxidant activity of silymarin and green tea extract are changed when they are given in combination to patients with chronic hepatitis C infection.
Read the detailed description
Silymarin and green tea are the two most widely used botanical products used by patients with chronic hepatitis C virus (HCV) infection. A major limitation of prior clinical investigations that may account for lack of efficacy is their use of inadequate customary oral dose regimens. Ongoing Phase II studies utilizing higher than customary doses of silymarin are based on potential disease modifying effects resulting from the potent antioxidant properties of silymarin flavonolignans. Since patients often use more than one herbal product to self-treat their disease, the use of higher than customary doses of silymarin may change silymarin's potential for herbal-herbal interactions. Pharmacokinetic interactions between silymarin and green tea catechins may change their safety/tolerability profiles, and may increase their antioxidant effects through additive or synergistic pharmacodynamic interactions. The objective of this double blind, active placebo controlled, randomized clinical trial is to characterize the pharmacokinetics and to evaluate the safety, tolerability, and antioxidant effects of an herbal cocktail consisting of silymarin and epigallocatechin gallate (EGCG) standardized green tea extract in treatment-naïve patients with chronic HCV infection. This investigation will include two treatment arms that will enroll 15 subjects per arm. Subjects will be randomized to receive in a fixed sequence either: 1) 196.5 mg EGCG followed by the coadministration of 700 mg silymarin; or 2) 700 mg silymarin followed by the coadministration of 196.5 mg EGCG. Each dosing regimen will be administered p.o. every 12 hrs for 12 days. No treatment arm uses high doses for both silymarin and EGCG in a sequence. Depending on the treatment arm, pharmacokinetic studies will be performed on plasma concentrations for six major silymarin flavonolignans and for the green tea catechin, EGCG at the end of 12 days of either silymarin or green tea extract monotherapy (Period 1), and then again after 12 days of silymarin and green tea extract given in combination (Period 2). For each treatment arm, plasma 8F2α-isoprostane concentrations, a measure of oxidative stress, will also be determined at baseline, during each period, and then at follow-up. The results from this investigation will be used to identify doses of silymarin and green tea that can be used together safely for future efficacy trials in patients with different chronic liver diseases.
- Conditions
- Chronic Hepatitis C, Oxidative Stress
- Being tested
- silymarin, green tea extract (EGCG)
- Keywords
- chronic hepatitis C, silymarin, green tea catechins, green tea extract, pharmacokinetics, antioxidant activity
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
silymarinDrug
Also called milk thistle
capsules, 700 mg, twice daily, 12 days
green tea extract (EGCG)Dietary supplement
Also called green tea catechins, EGCG
capsules, 196.5 mg, twice daily, 12 days
| Study group | Role | What they receive |
|---|---|---|
| low dose silymarin and low dose EGCG | Experimental | Not described Receives: Drug: silymarin; Dietary Supplement: green tea extract (EGCG) |
| high dose silymarin and low dose EGCG | Experimental | Not described Receives: Drug: silymarin; Dietary Supplement: green tea extract (EGCG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability of coadministered silymarin and green tea extract at different doses in patients with chronic hepatitis C.
Measured: November 2009 to September 2012
Secondary outcomes (1)
To characterize the antioxidant effects of silymarin and EGCG administered alone or in combination.
Measured: November 2009 to September 2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionApr 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Roy L Hawke, PhD, PharmD, Principal investigator, UNC School of PharmacyMichael W Fried, MD, Study chair, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01018615
- Sponsor's protocol ID
- 08-1631
- Other IDs
- R21AT003892-01A2, CTRC-2779
- Status last verified
- Jun 2014
- First submitted
- 20 Nov 2009
- Last updated
- 18 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Steady-State Pharmacokinetic Interactions of Green Tea Catechins and Silymarin Flavonolignans in Treatment Naïve Patients With Chronic Hepatitis C Infection
- ClinicalTrials.gov ID
- NCT01018615
- Acronym / sponsor ID
- 08-1631
- Conditions
- Chronic Hepatitis C, Oxidative Stress
- Keywords
- chronic hepatitis C, silymarin, green tea catechins, green tea extract, pharmacokinetics, antioxidant activity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH)
- Study start
- Nov 2009
- Primary completion
- Apr 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 23 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if the safety, metabolism, and antioxidant activity of silymarin and green tea extract are changed when they are given in combination to patients with chronic hepatitis C infection.
Detailed description
Silymarin and green tea are the two most widely used botanical products used by patients with chronic hepatitis C virus (HCV) infection. A major limitation of prior clinical investigations that may account for lack of efficacy is their use of inadequate customary oral dose regimens. Ongoing Phase II studies utilizing higher than customary doses of silymarin are based on potential disease modifying effects resulting from the potent antioxidant properties of silymarin flavonolignans. Since patients often use more than one herbal product to self-treat their disease, the use of higher than customary doses of silymarin may change silymarin's potential for herbal-herbal interactions. Pharmacokinetic interactions between silymarin and green tea catechins may change their safety/tolerability profiles, and may increase their antioxidant effects through additive or synergistic pharmacodynamic interactions. The objective of this double blind, active placebo controlled, randomized clinical trial is to characterize the pharmacokinetics and to evaluate the safety, tolerability, and antioxidant effects of an herbal cocktail consisting of silymarin and epigallocatechin gallate (EGCG) standardized green tea extract in treatment-naïve patients with chronic HCV infection. This investigation will include two treatment arms that will enroll 15 subjects per arm. Subjects will be randomized to receive in a fixed sequence either: 1) 196.5 mg EGCG followed by the coadministration of 700 mg silymarin; or 2) 700 mg silymarin followed by the coadministration of 196.5 mg EGCG. Each dosing regimen will be administered p.o. every 12 hrs for 12 days. No treatment arm uses high doses for both silymarin and EGCG in a sequence. Depending on the treatment arm, pharmacokinetic studies will be performed on plasma concentrations for six major silymarin flavonolignans and for the green tea catechin, EGCG at the end of 12 days of either silymarin or green tea extract monotherapy (Period 1), and then again after 12 days of silymarin and green tea extract given in combination (Period 2). For each treatment arm, plasma 8F2α-isoprostane concentrations, a measure of oxidative stress, will also be determined at baseline, during each period, and then at follow-up. The results from this investigation will be used to identify doses of silymarin and green tea that can be used together safely for future efficacy trials in patients with different chronic liver diseases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| low dose silymarin and low dose EGCG | Experimental | Drug: silymarin, Dietary Supplement: green tea extract (EGCG) |
| high dose silymarin and low dose EGCG | Experimental | Drug: silymarin, Dietary Supplement: green tea extract (EGCG) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects will be eligible for enrollment in this study if they meet the following criteria:
- Males or females; age at least 18 years at screening
- Negative urine pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of silymarin. Females of childbearing potential must be using two reliable forms of effective contraception during the study (while on drug and during follow-up)
- Hepatitis C virus (HCV) patients
- Any HCV genotype
Key exclusion criteria (24 listed)
- Use of other milk thistle or green tea preparations within 30 days of Study Visit 1 (Day 1)
- Use of other antioxidants such as vitamin E, vitamin C, glutathione, alpha-tocopherol, within 30 days of Study Visit 1 (Day 1). A multivitamin at standard doses will be allowed.
- Use of diets containing > 6 servings per day, or 4-6 servings per day from > 8 of the vegetables and fruits listed in Appendix 2.
- Allergy/sensitivity to milk thistle, green tea or their preparations
- Inability to tolerate milk products (lactose intolerant)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| silymarinAlso: milk thistlecapsules, 700 mg, twice daily, 12 days | Drug | high dose silymarin and low dose EGCG, low dose silymarin and low dose EGCG |
| green tea extract (EGCG)Also: green tea catechins, EGCGcapsules, 196.5 mg, twice daily, 12 days | Dietary supplement | high dose silymarin and low dose EGCG, low dose silymarin and low dose EGCG |
Primary outcome
To assess the safety and tolerability of coadministered silymarin and green tea extract at different doses in patients with chronic hepatitis C.
Time frame: November 2009 to September 2012
1 secondary outcome
To characterize the antioxidant effects of silymarin and EGCG administered alone or in combination.
Time frame: November 2009 to September 2012
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roy L Hawke, PhD, PharmD principal investigator
UNC School of Pharmacy
Michael W Fried, MD study chair
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing silymarin and green tea extract (EGCG) in people with Chronic Hepatitis C and Oxidative Stress, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety and tolerability of coadministered silymarin and green tea extract at different doses in patients with chronic hepatitis C. (time frame: November 2009 to September 2012). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2017.